Catalytic Regioselective Acylation of Unprotected Nucleosides for Quick Access to COVID and Other Nucleoside Prodrugs

被引：9

作者：

Lv, Jie ^{[1
]}

Zou, Juan ^{[2
]}

Nong, Yingling ^{[1
]}

Song, Jia ^{[1
]}

Shen, Tingwei ^{[1
]}

Cai, Hui ^{[1
]}

Mou, Chengli ^{[2
]}

Lyu, Wenxin ^{[3
]}

Jin, Zhichao ^{[1
]}

Chi, Yonggui Robin ^{[1
,3
]}

机构：

[1] Guizhou Univ, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr Bioengn, Minist Educ, Guiyang 550025, Peoples R China

[2] Guizhou Univ Tradit Chinese Med, Sch Pharm, Guiyang 550025, Peoples R China

[3] Nanyang Technol Univ, Sch Chem Chem Engn & Biotechnol, Singapore 637371, Singapore

来源：

ACS CATALYSIS | 2023年 / 13卷 / 14期

基金：

中国国家自然科学基金; 新加坡国家研究基金会;

关键词：

pentose functionalization; regioselective; nucleosides; antiviral drug synthesis; organocatalysis; HEPATITIS-C; VIRUS-S; RIBAVIRIN; NUCLEOTIDES; MOLNUPIRAVIR; ELIMINATION; DERIVATIVES; INHIBITORS; EIDD-2801; MK-4482;

D O I：

10.1021/acscatal.3c02069

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Nucleosides have important therapeuticapplications thatincludeantiviral activities against COVID viruses. It is a common strategyto convert one or multiple of the hydroxyl (OH) units in nucleosidesto the corresponding ester groups to prepare nucleoside prodrugs forbetter performance. Due to the presence of multiple OH units in nucleosides,current protocols for access to such ester prodrugs involve multiplesteps due to installation and removal of protection groups. Here,we disclose a catalytic strategy that allows for regioselective functionalizationof a specific OH unit without the need of protecting other OH groups.The key step in our method is an N-heterocyclic carbene-catalyzedselective acylation of the pentose unit of nucleosides. We demonstratethat commercially launched COVID-19 prodrugs such as molnupiravircan be prepared in concise routes by using our strategy.

引用

页码：9567 / 9576

页数：10

共 69 条

[1] Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine [J].